Our discovery that dibutyryl cyclic AMP, dose-relatedly, shortens narcosis induced by eight structurally different central nervous system (CNS) depressants led to our findings of the antidotal properties of the nucleotide. Rats and monkeys overdosed with a lethal dose (LD100) of amobarbital survive when dibutyryl cyclic AMP is injected intracerebroventricularly (ICV), suggesting that the nucleotide is 1) devoid of toxicity; 2) acts on the CNS target cells; and 3) CNS depression is the major cause of death. In rats and monkeys we will determine: acute, subacute and long term toxicity; relative efficacy of various modes of administration of the barbiturates; correlation between concentrations of amobarbital and cyclic AMP in the blood, cerebrospinal fluid (CSF) and brain tissues and clinical parameters such as: electrocardiogram, electroencephalogram, CSF pressure, temperature and respiration; time intervals within which dibutyryl cyclic AMP must be administered to afford protection and prevent brain tissue damage. This information will ultimately lead to the establishment of dose ranges for the various degrees of drug overdosage. An acute 30 day toxicity study of dibutyryl cyclic AMP in the rat and the delayed-response test in the monkey should support our contention that the nucleotide is a true antidote to amobarbital overdosage.